Circulating tumor DNA (ctDNA) is a promising biomarker for noninvasive diagnostic, prognostic, and follow-up tests for cancer. However, the relatively low quantity of ctDNA and the rare cancer mutations within large excess of wild-type DNAs have presented many challenges for its application in the clinic. The goal of the research is to develop our magnetic nanobeads and highly fluorescent magnetic nanoparticles enabled automatic sample preparation and diagnostic assay technology for ctDNA diagnostics. Our magnetic ctDNA extraction technology offers higher yield and quality of extracted ctDNA compared to maket standard; our magnetic DNA sizing beads ensure DNA library with higher yield and cleanness for better NGS data; the magnetic automation will improve assay throughput, consistency and save cost; and the HFMN gene mutation detection assay provides the opportunity for faster and more economic mutation detection for physician to make discrete treatment management. The ctDNA diagnostics to be developed through this project can be applied for roughly 70% of breast cancer patients who were subtyped ER+/Her2- and treated with endocrine therapy, at time of relapse, for physicians to make personalized treatment decisions that can lead to more effective outcome. Once successfully established, our ctDNA diagnostic platform can be expanded to multiple other cancer types, using circulating nucleic acids as reliable biomarkers for earlier cancer detection, patient stratification, and serial monitoring of cancer treatment, and improving treatment for millions of cancer patients.